Dialytic removal of fluid, potassium and acid is life-saving in individuals with hemodialysis (HD)-dependent end stage renal disease. However, there is compelling evidence that the dialysis procedure contributes to the risk of serious arrhythmias including sudden cardiac arrest (SCA)?which accounts for roughly 25% of all deaths in HD patients and occurs at a rate 20x that in the general population?and atrial fibrillation (AF)?a highly prevalent condition in HD strongly associated with cardiovascular morbidity, mortality and stroke. Specifically, there are strong and consistent observations linking the dialytic fluid ultrafiltration (UF) rate as well as serum and dialysate potassium and bicarbonate concentrations to fatal and non-fatal arrhythmia. Given the high rates of cardiovascular morbidity and mortality in HD patients and the evidence that standard cardiovascular therapies are ineffective, designing prospective, randomized trials to investigate whether changes to current treatment paradigms regarding modifiable facets of the dialysis prescription will reduce the risk of arrhythmic events represents a novel approach with the strong potential to reduce mortality. Historically, such studies have been unfeasible due to the limits of long-term electrocardiographic monitoring, but new technologies have overcome this challenge: Our unique experience with novel implantable loop recording (ILR) technology in HD patients, and our expertise in HD patient-oriented studies place us in the optimal position to conduct randomized, crossover trials leveraging point of care (POC) electrolyte testing with ILR technology in order to compare the long-term impact of 3 randomized manipulations of the dialysis prescription on arrhythmia: low vs. high serum to dialysate potassium gradient, low vs. high serum-dialysate bicarbonate gradient, and low vs. high ultrafiltration (UF) rates. Our proposed trials will transform understanding of how dialysis prescriptions impact HD-associated arrhythmia and will directly influence clinical care. The current application seeks support under the R34 mechanism to conduct pilot trials designed to: Test the feasibility of POC-guided dialysate potassium and bicarbonate prescriptions as well as the feasibility of limiting UF rate in an HD trial (Aim 1); Analyze recruitment feasibility for trials combining ILR insertion to monitor arrhythmia with POC-guided bicarbonate or potassium prescriptions or UF rate manipulation (Aim 2); and Refine effect estimates for change in arrhythmia frequency with each intervention (Aim 3). These studies will provide unique data on the causal role of dialysis in HD-associated arrhythmia and the information necessary for the design of definitive, large- scale interventional trials with the potential to transform dialysis.